Resistance to trophic neurite outgrowth of sensory neurons exposed to insulin
Autor: | Yongqin Xu, Bhagat Singh, Jose A. Martinez, Vandana Singh, Douglas W. Zochodne, Anand Krishnan, Todd McLaughlin |
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Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
biology Neurite Insulin medicine.medical_treatment Type 2 Diabetes Mellitus medicine.disease Biochemistry Sensory neuron Cellular and Molecular Neuroscience Insulin receptor medicine.anatomical_structure Insulin resistance Endocrinology Diabetes mellitus Internal medicine biology.protein medicine Receptor |
Zdroj: | Journal of Neurochemistry. 121:263-276 |
ISSN: | 0022-3042 |
Popis: | J. Neurochem. (2012) 121, 263–276. Abstract Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2-h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down-regulated mRNAs of the insulin receptor β subunit and up-regulated levels of GSK-3β, both potential mechanisms of insulin resistance, while down-regulating the protein expression of pAkt and pGSK-3β. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin-induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders. |
Databáze: | OpenAIRE |
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